Role of Ligands in the Uptake and Reduction of V(V) Complexes in Red Blood Cells

The interaction with erythrocytes
of four [VVO2L2]− complexes, with L = picolinate
(pic), 5-cyanopicolinate (picCN), 3-aminopyrazine-2-carboxylate (przNH2), and 1,2-dimethyl-3-hydroxy-4­(1H)-pyridinonate
(dhp), was studied. The thermodynamic stability at physiological pH
is: [VVO2(dhp)2]− > [VVO2(przNH2)2]− > [VVO2(pic)2]− > [VVO2(picCN)2]−. With picCN and pic, V exists at physiological
pH
as H2VVO4–, with
przNH2 as a mixture of H2VVO4– and [VVO2(przNH2)2]− and with dhp as [VVO2(dhp)2]−. In the systems
with pic and picCN, H2VVO4– and the ligands cross the erythrocyte membrane independently, with
dhp the uptake occurs by diffusion, whereas with przNH2 both the mechanisms are active. Inside erythrocytes stable VIVOL2 complexes are formed, indicating that there
is no relationship with the stability and redox state of the administered
compounds and that, if the metal ion changes its oxidation state in
the cytosol as V does, unstable complexes in the extracellular medium
could become stable inside the cells and contribute to the pharmacological
action.